Efficacy and Safety of Depemokimab (GSK3511294) in Participants With Chronic Rhinosinusitis With Nasal Polyps (ANCHOR-2)

Inclusion Criteria:

Inclusion Criteria:

• Participants with 18 years of age and older inclusive, at the time of signing theinformed consent.

• Endoscopic bilateral NP score of at least 5 out of a maximum score of 8 (with aminimum score of 2 in each nasal cavity) assessed by the investigator.

• Participants who have had at least one of the following at Visit 1: Previous nasalsurgery for the removal of NP; Have used at least three consecutive days of systemiccorticosteroids in the previous 2 years for the treatment of NP; Medicallyunsuitable or intolerant to systemic corticosteroid.

• Participants (except for those in Japan) must be on daily treatment with intranasalcorticosteroids (INCS) (including intranasal liquid steroid wash/douching) for atleast 8 weeks prior to screening.

• Participants presenting with severe NP symptoms defined as symptoms of nasalcongestion/blockade/obstruction with moderate or severe severity and loss of smellor rhinorrhea (runny nose) based on clinical assessment by the investigator.

• Presence of symptoms of chronic rhinosinusitis as described by at least 2 differentsymptoms for at least 12 weeks prior to Visit 1, one of which should be either nasalblockage/obstruction/congestion or nasal discharge (anterior/posterior nasal drip),plus facial pain/pressure and/or reduction or loss of smell.

• Male or eligible female participants

Exclusion Criteria:

Exclusion Criteria:

• As a result of medical interview, physical examination, or screening investigationthe physician responsible considers the participant unfit for the study.

• Cystic fibrosis.

• Antrochoanal polyps.

• Nasal cavity tumor (malignant or benign)

• Fungal rhinosinusitis

• Severe nasal septal deviation occluding one nostril preventing full assessment ofnasal polyps in both nostrils.

• Participants who had a sino-nasal or sinus surgery changing the lateral wallstructure of the nose making impossible the evaluation of nasal polyp score.

• Acute sinusitis or upper respiratory tract infection (URTI) at screening or in 2weeks prior to screening.

• Ongoing rhinitis medicamentosa (rebound or chemical induced rhinitis).

• Participants who have had an asthma exacerbation requiring admission to hospitalwithin 4 weeks of Screening.

• Participants who have undergone any intranasal and/or sinus surgery (for examplepolypectomy, balloon dilatation or nasal stent insertion) within 6 months prior toVisit 1; nasal biopsy prior to Visit 1 for diagnostic purposes only is excepted.

• Participants where NP surgery is contraindicated in the opinion of the Investigator.

• Participants with other conditions that could lead to elevated eosinophils such ashyper-eosinophilic syndromes including (but not limited to) eosinophilicgranulomatosis with polyangiitis (EGPA) (formerly known as Churg-Strauss Syndrome)or Eosinophilic Esophagitis.

• Participants with a known, pre-existing parasitic infestation within 6 months priorto Visit 1.

• A known immunodeficiency (e.g. human immunodeficiency virus (HIV), other than thatexplained by the use of corticosteroids (CSs) taken as therapy for asthma.

• A current malignancy or previous history of cancer in remission for less than 12months prior to screening.

• Liver Disease: Alanine aminotransferase (ALT) >2 times upper limit normal (ULN);Total bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable ifbilirubin is fractionated and direct bilirubin less than [<]35 percent [%]);Cirrhosis or current unstable liver or biliary disease per investigator assessmentdefined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia,esophageal or gastric varices, persistent jaundice.

• Participants who have known, pre-existing, clinically significant cardiac,endocrine, autoimmune, metabolic, neurological, renal, gastrointestinal, hepatic,hematological or any other system abnormalities that are uncontrolled with standardtreatment.

• Participants with current diagnosis of vasculitis. Participants with high clinicalsuspicion of vasculitis at screening will be evaluated and current vasculitis mustbe excluded prior to enrollment.

• Hypersensitivity: Participants with allergy/intolerance to the excipients ofdepemokimab (GSK3511294) in a monoclonal antibody, or biologic.

• Participants that, according to the investigator's medical judgment, are likely tohave active Coronavirus disease-2019 (COVID-19) infection must be excluded.Participants with known COVID-19 positive contacts within the past 14 days must beexcluded for at least 14 days following the exposure during which the participantshould remain symptom-free. Reported smell/ taste complications from COVID-19 mustbe used as exclusion.

• Participants that have been exposed to ionising radiation in excess of 10millisievert (mSv) above background over the previous 3-year period as a result ofoccupational exposure or previous participation in research studies.

• Previously participated in any study with mepolizumab, reslizumab, or benralizumaband received study intervention (including placebo) within 12 months prior to Visit

• Women who are pregnant or lactating or are planning on becoming pregnant during thestudy.